By Jamie Su
Beta-thalassemia is a genetic blood disorder caused by mutations in the production of beta-globin that reduce the production of hemoglobin. If left untreated, beta-thalassemia can result in organ failure and death. Most patients with this disease do not live over the age of 30.
Current treatments for beta-thalassemia all have moderate to severe setbacks. The most severe form of the disease, beta-thalassemia major, requires blood transfusion therapy. Blood transfusions are the most common type of treatment for this disease, yet they often result in iron overload. An alternative is taking folic acid supplements, which prevent iron overload, but can cause nausea and loss of appetite. More recently, the clinical use of luspatercept to treat thalassemia has been increasing. Luspatercept is often used to treat anemia and involves an injection for red blood cells. However, the side effects include severe headaches and dizziness.
Alternatively, there is the option of bone marrow and stem cell transplants. This is a process in which healthy stem cells are transferred to the blood-producing tissue located in the bone marrow of the patient. So far, this is the best known cure for thalassemia, but if anything, the risks are the highest. First and foremost, it is difficult to find a compatible donor for the stem cell transplant. Many patients could wait for years before the right match comes along. If a healthy donor is found, the patient must know and understand the risk of Graft vs. Host disease (GVHD).
GVHD occurs when the donated stem cells see the patient’s cells as foreign and attack them. Acute GVHD (aGVHD) occurs shortly after treatment, while chronic GVHD (cGVHD) typically occurs two years after treatment. Symptoms of aGVHD typically target the skin as rashes but can also include diarrhea, nausea and vomiting, abdominal cramping, and jaundice. Symptoms of cGVHD target the skin, liver, gastrointestinal tract, and lungs, but can even cause hair loss, mouth sores, gum disease, and fatigue.
A Hopeful Future With CRISPR
CRISPR-Cas9 is a gene editing therapy that edits DNA at precise locations, designed by modifying a natural bacterial process. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, a family of genes that act as a bacterial defense system, while a Cas9 nuclease is an engineered protein that cuts DNA. In December 2023, the FDA approved the first gene therapies for treating sickle cell disease. This is a huge milestone, not only for sickle cell disease, but for rare diseases as a whole.
Beta-thalassemia is caused by mutated beta-globin DNA. CRISPR is able to correct the mutated gene. Guide RNA (gRNA) is engineered to direct CRISPR-Cas9. Together, the gRNA and Cas9 form a ribonucleoprotein complex (RNP). The Cas9 binds and cuts the target at the protospacer adjacent motif sequence (PAM) site. Currently, in initial cellular studies, the efficiency of the RNP must be quantified by extracting DNA two to three days after the RNP is introduced. Polymerase chain reaction (PCR) is then used to amplify the area, creating additional DNA which is used to determine the on-target cutting efficiency.
CRISPR-Cas9 for beta thalassemia must pass the clinical trials, which include determining a safe dosage, assessing the effectiveness of the treatment, and comparing it to current treatments. Finally, it will await FDA approval.
With the approval of CRISPR for sickle cell disease, we might not be waiting for long.
Astra Stem 
Leave a comment